Methicilin-susceptible S.aureus bacteraemia. MedDRA version: 20.0 Level: LLT Classification code 10058863 Term: Staphylococcus aureus bacteraemia System Organ Class: 100000004862
Conditions
Interventions
Product Name: CLOXACILINA
Pharmaceutical Form: Concentrate and solvent for solution for infusion
INN or Proposed INN: CLOXACILLIN
CAS Number: 61-72-3
Sponsors
Miquel Pujol i Rojo ( Servicio de Enfermedades Infecciosas del Hospital Universitari de Bellvitge
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) 18 years of age or over. 2) Patients hospitalised with 1 or more MSSA-positive blood cultures obtained within the 72 hours prior to inclusion in the study, in a context suggesting an infection. 3) The subject or their legal representative grants informed consent. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 150 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 150
Exclusion criteria
Exclusion criteria: 1) Compromised clinical situation with a life expectancy of = 24 h. 2) Resistance to fosfomycin. 3) Severely impaired liver function (Child-Pugh grade C). 4) NYHA scale III-IV heart failure. 5) Need for concomitant antibiotic therapy together with the study antibiotics for the first 7 days of the study, active against S. aureus. 6) Hypersensitivity to cloxacillin or to beta-lactams in general or to fosfomycin. 7) Polymicrobial bacteremia. 8) Participation in another clinical therapy trial. 9) Previous participation in the present clinical trial. 10) Myasthenia gravis 11) Pregnancy and lactation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: We established two primary object. with hierarchical testing: 1) First primary endpoint: Early success of therapy defined by all of the following criteria met after randomization: - Patient alive at day 7; Clinical success defined as clinical improvement measured by stable or improved quick SOFA score (compared with baseline) AND fever resolved at day 7; Blood cultures negative for S. aureus at day 7. No isolation of S. aureus in another sterile site from day 8 until TOC visit at 12 weeks after random allocation. 2) Second primary endpoint: Success of therapy is defined at TOC by presence of all of the following (“long time success”): Patient alive at 12 weeks after random allocation; No isolation of S. aureus from sterile site (e.g. blood, joint fluid, tissue) > 14 days from randomization until TOC visit at 12 weeks after random allocation. For both endpoints the use of an additional MSSA-active iv antibiotic until day 7 will be considered as treatment failure (“no success”). ; Secondary Objective: 1)Clinical Obj:All-cause mortality at different visits.Persistent bacteraemia at 3 and 7 days after random allocation.Microbiological relapse as defined by (at least one)positive blood culture for MSSA at least 72h after a preceding negative culture.Complicated bacteraemia.Duration of intravenous antibiotic treatment.Length of stay in hospital.Microbiological secondary endpoints.Pharmacologic secondary endpoints.Sub group analysis for patients at high risk.2)Microbiological Obj:To establish duration of bacteraemia,persistent and recurrent bacteraemia.Emergence of fosfomycin resistance.To establish functionality of agr operon and its relationships with changes in vancomycin (VAN) and daptomycin(DAP) MIC and biofilm production.To establish"in vitro"synergy of clox-fos combinations.Sequencing of complete bacterial genome and changes in patients with therapeutic failure3)Pharmacodynamic Obj:To det | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Clinical: 1.1) All-cause mortality at days 7, 14, EOT after random allocation. 1.2) Number of patients withdrew from the study. 1.3) Persistent bacteraemia (at least one positive blood culture) at day 3 and at day 7 1.4) Recurrent bacteraemia during the study period. 1.5) Patients with persistent and recurrent bacteraemia. 1.6) Number of patients with complicated bacteraemia 1.7) Duration of intravenous antibiotic treatment. 1.8) Length of stay in intensive care unit and in hospital, clinical success at day 3, 7, and the end of the antibiotic study treatment (EOT) and test of cure visit (TOC). 1.9) Sub group analysis for patients at high risk. 2)Microbiological: 2.1) Resistance to fosfomycin during treatment; 2.2) Minimum inhibitory concentration (MIC) for vancomycin, daptomycin, dalvabancin and its relationship with MSSA complications; 2.3) Accessory gene regulator (agr) polymorphism; 2.4) “In vitro” synergy between cloxacillin-fosfomycin; 2.5) Whole genome sequencing and association of genome changes and patients with therapeutic unsuccessful. 3) Pharmacokinetics: 3.1) Minimum concentration (Cmin.), 3.2) Mid-dosing interval concentration and maximum concentration (Cmax.) reached at the different sampling times. 3.3) Relationship between PK variables and efficacy. 4) Security: 4.1) Incidence of adverse events, serious adverse events, adverse drug reactions, dropouts and its relationship with the study treatment. ;Timepoint(s) of evaluation of this end point: Secondary variables will be evaluated in different moments depending on each variable definition | — |
Countries
Spain
Contacts
Public ContactHospital Universitari de Bellvitge
Miquel Pujol i Rojo ( Servicio de Enfermedades Infecciosas del Hospital Universitari de Bellvitge
Outcome results
None listed